Our research is designed to see whether or not any general rules govern the recognition of transfer RNA by its cognate amino acid:tRNA ligase. Our approach is based on the rationale that this recognition process is determined ultimately by the nucleotide sequence of the tRNA. Therefore, alteration of this sequence in a known manner provides a method for locating the residues that play a role in the recognition process. Using C yields U transitions induced by bisulfite ions to probe for structure-action relationships, we are attempting to answer the following questions: (1) Where is the specific recognition site located in the tRNA? (2) Is the same region involved in different tRNAs? (3) Do certain areas influence the kinetics but not the specificity of aminoacylation? (4) How do mutations that produce C yields U transitions at different positions in the tRNA influence the kinetics and specificity of aminoacylation? (5) Can well-characterized missense and nonsense suppressor tRNA be produced by purely chemical procedures? In order to answer these questions, we have begun a systematic study of ten tRNAs in which a C yields U transition in the anticodon represents a missense change. If successful, our work should provide a better understanding of the fundamental role that transfer RNA plays in the specificity and control of genetic expression.